Trevena has announced that it has successfully completed a phase 2a study on the haemodynamic effects of TRV027 in patients with advanced heart failure with reduced ejection fraction. TRV027 was generally well-tolerated in this study and produced beneficial haemodynamic effects in line with those observed in previously published pre-clinical studies.
Trevena is developing TRV027 for the intravenous hospital treatment of acute decompensated heart failure, and these data support the advancement of TRV027 into a future study to evaluate its clinical efficacy in patients suffering with acute heart failure.
“The data from this study suggest that TRV027 is safe, and that its pharmacology in patients with heart failure is consistent with that shown in preclinical studies. We are looking forward to studying the effects of this exciting new therapy in patients suffering with acute heart failure, where we desperately need new therapeutic alternatives,” said G. Michael Felker, associate professor of Medicine at Duke University and member of the steering committee for clinical development of TRV027.
The phase 2a study is a randomised, double-blind, placebo-controlled, adaptive, ascending dose-titration study to evaluate the safety, tolerability, pharmacokinetics, and invasive haemodynamics of TRV027 in patients with stable NYHA Class 3 and 4 heart failure. Thirty-three catheterised patients were enrolled at centres in the USA and Europe. Twenty-four patients received TRV027 and 9 patients received placebo.
TRV027 rapidly and reversibly decreased both blood pressure and pulmonary capillary wedge pressure, which is linked to dyspnea in acute heart failure. In the background of these blood pressure effects, TRV027 preserved kidney function, as measured by creatinine and cystatin C, which is of critical importance in acute heart failure. TRV027 also preserved cardiac output. No drug-related serious adverse events were reported, consistent with the safety profile seen in preclinical studies. These findings demonstrate the safety and anticipated pharmacology of TRV027 in patients with advanced heart failure.
